These are exciting times for the field of gene therapy. Various vector systems derived from naturally occurring viruses have moved to the clinic and are being used to treat human diseases as diverse as blindness, hemophilia and other hematopoietic disorders, and cancer. Despite these successes, there remains strong interest in developing nonviral vector systems with the aim of both reducing cost of therapy and mitigating toxicities, immunological side effects, and other adverse events that have occasionally been encountered with viral systems. A key mission of the Molecular Therapy family of journals—and our parent Society—is to provide a forum for presentation of emerging novel technologies for delivery of the broad spectrum of molecular therapies. It is with this in mind that we published our first Special Issue this past March, on the topic of gene editing technology and applications. Field leaders contributed cutting-edge reviews and original research on this powerful and rapidly evolving new technology. The papers are receiving robust citations and downloads, attesting to the strong interest among our readers and in the field overall.
We are therefore thrilled to announce our second Special Issue, on the topic of nanoparticle development and applications in gene and cell therapy, to coincide with the 19th Annual Meeting of the ASGCT in May 2017. Nanoparticulate drug carriers and multifunctional nanoconstructs are finding increasing application in the development of cellular and molecular therapies. Nanoparticles are being engineered for controlled targeting and delivery of therapeutic agents at specific physiological sites, for in situ biological sensing (e.g., compartmental pH monitoring), and diagnostic imaging. At the same time, engineered nanoparticles can act as tools for modulating intracellular processes, facilitating study of the dynamic and integrated biochemical processes that contribute to the underlying pathogenesis of disease. Advances in material sciences have further provided myriad inorganic, organic, and composite nanosystems with exciting biophysical properties. Indeed, we have learned a great deal about how nanoparticle parameters such as shape, size, and surface characteristics modulate their biological performance.
However, there remains much to be done with regard to optimization of such systems for particular physiological and therapeutic needs, particularly with respect to the type, developmental stage, and location of the disease target and the distinct biological barriers encountered at the different stages of nanoparticle targeting and delivery. This optimization should allow eventual translation into better design and engineering of safe and efficient nanopharmaceuticals and may even find application in optimization of virus-based vectors.
Optimization of these systems will require further improvement of animal models representing human diseases to overcome efficacy and safety shortcomings observed in clinical trials. Furthermore, the empirical approaches often employed in nanocarrier development must be replaced by integrated “structure–activity” mapping at the single-cell, organelle, and molecular levels for better understanding of mechanistic issues. This also requires development of new and robust methodologies for precision screening. In addition, we must develop an extensive computational network knowledge of genomic and epigenomics of interindividual variations in nanopharmaceutical performance and adverse responses before pushing the boundaries of the envisaged nanotherapies to a personalized level. Finally, the proof of concept in biological targeting is not sufficient on its own; precision characterization of nanotherapeutic components is essential and should include the biophysical state of the therapeutic cargo. After all, a successful nanopharmaceutical must be structurally simple with attributes that will enable production of an affordable, viable, and clinically acceptable formulation.
It is with such intentions that this Special Issue of Molecular Therapy will delve into recent advances in fundamental and translational aspects of nanoparticles in cell and molecular therapies as well as calling for a paradigm shift in the design of high-performance nanopharmaceuticals through a pan-integrated molecular bioscience and systems approach. Accordingly, we strongly encourage submission of interdisciplinary topical research, commentaries, and opinion pieces addressing these topics. This call for papers remains open until 1 December 2016 for rapid review and consideration for publication in this exciting collection. Potential contributors are encouraged to contact Guest Editors Moien Moghimi and Ernst Wagner or other members of the Molecular Therapy editorial team for rapid consideration and feedback.